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Comparison between structures of human, mouse and rat P2X7 receptors define ortholog-specific pharmacology and facilitated structure-based drug design of UB-MBX-46, an antagonist that selectively inhibits the human P2X7 receptor with sub-nanomolar potency.

The extracellular matrix provides a critical scaffold for the epidermal layers of the skin. Here, He and Boraas et al. discover that the foundation for resilient skin healing in embryos lies in the supportive matrix beneath stem cells.

Understanding the mechanisms behind clinical immunity to malaria is crucial for developing effective interventions. Here, the authors demonstrate that clinical immunity to Plasmodium vivax develops rapidly after a single controlled human malaria infection, reducing inflammatory responses and protecting against symptoms, while not significantly affecting parasite load.

Telomere fusions are linked to oncogenesis in multiple cancer types, but their patterns are poorly understood. Here, the authors use whole-genome sequencing data to compare fusion events across cancer types, and identify a novel type of telomere fusion pattern associated with the Alternative Lengthening of Telomeres (ALT) pathway that can be used for liquid biopsy analysis.

In cancer cells, telomeres can be elongated through homology directed-repair pathways in a process known as Alternative Lengthening of Telomeres (ALT). Here, the authors reveal that FANCM regulates ALT activity and ALT cell proliferation by limiting the activity of uncontrolled BLM and telomeric R-loops.

In the double-blind, placebo-controlled phase 2 ARGO trial, patients with active psoriatic arthritis treated with a nanobody targeting IL-17A and IL-17F showed substantially better disease response rates compared with those receiving placebo treatment.

Proteomic definition of the telomeric PARylome combined with genetic and histone H3.3 deposition assays at telomeres reveals that PAR-regulated HIRA activity compensates for loss of ATRX in ALT cells.

Circulating liver enzymes, like alanine aminotransferase (ALT) and aspartate aminotransferase (AST), are highly heritable and predictive of disease. Here, the authors perform a genome-wide association study on ALT and AST, revealing a rare variant in SLC30A10 associated with elevated ALT and AST.

This study reports that the gene SMPED1, located in a previously identified dichogamy-determining region in Alpinia species, controls the timing of sex-organ synchrony, improving our understanding of the evolutionary mechanisms of plant sexual diversity.

TERRA RNA has previously been linked to Alternative lengthening of telomeres (ALT). Here the authors developed a tool to rapidly inhibit TERRA transcription from different chromosome ends in an ALT cell line to show that TERRA transcription actively promotes break induced replication (BIR) and destabilizes telomere integrity in ALT cells.

Chronic alcohol use in humans and mice downregulates small intestinal mAChR4 and reduces goblet-cell-associated antigen passage formation, disrupting antimicrobial immunity.

Transcriptome-scale maps of RNA secondary structure ensembles in living cells detect candidate RNA structural switches.

The quark structure of the f₀(980) hadron is still unknown after 50 years of its discovery. Here, the CMS Collaboration reports a measurement of the elliptic flow of the f₀(980) state in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of 8.16 TeV, providing strong evidence that the state is an ordinary meson.

McCreery, Stubb et al. show that mechano-osmotic changes in the nucleus induce general transcriptional repression and prime chromatin for cell fate transitions by relieving repression of specific differentiation genes.

Mutations of ATRX are frequent in cancers that immortalize through the ALT (Alternative lengthening of telomeres) pathway. Here the authors show that ALT features are repressed in embryonic stem cells that lack ATRX but induced by continuous telomere instability triggered upon cell differentiation.

The authors provide a comprehensive characterization of how glutamine uptake and utilization regulate macrophage function in atherosclerosis.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

How age affect the immune response to malaria is not fully understood. Here, the authors characterise the transcriptome and serum inflammatory cytokines in children and adults in response to malaria, showing that there is an increase of inflammatory chemokine and cellular responses in adults compared to children.

In a randomized, placebo-controlled, stepwise dose-escalation phase 1 trial evaluating a conjugate vaccine against both typhoid and invasive non-typhoidal Salmonella infections, the vaccine was found to be safe and immunogenic in healthy adults.

The gut microbiota can influence the severity of pneumonia through the production of metabolites. In this translational study, the authors investigate the effects of tryptophan metabolites, specifically indole-3-acetic acid (IAA), on pneumonia.

The regulatory landscape controlling Hoxd gene expression in tetrapod digit development was probably co-opted from a pre-existing cloacal regulatory mechanism, as evidenced by the effects of genetic deletion experiments in zebrafish fin, cloaca and mouse urogenital development.

Telomerase-independent telomere lengthening is a potential target for cancer therapy, but molecules specific to this pathway have remained elusive. Henson et al. show that DNA circles of (CCCTAA)_n are specific intermediates of alternative lengthening of telomeres and present a sensitive assay to detect them.

CAR-T cells engineered with αPD-L1–IL-12 fusion proteins show antitumour activity in mouse models of prostate and ovarian cancer.

Here the authors report that hepatic loss of GTPase-activating protein-binding protein1 (G3BP1) exacerbates MASLD and MASH pathogenesis in a study with male mice. Mechanistically, G3BP1 interacts with SNARE proteins and promotes autophagosome-lysosome fusion, and facilitates nuclear translocation of the transcription factor TFE3.

Genomic integration of DNA templates is made more precise through microhomology-focused design.

There is an unmet clinical need for a rapid point-of-care tests to identify patients at high-risk of developing acute liver failure following a paracetamol overdose. Here, authors assess a diagnostic test, consisting of a lateral flow immunoassay paired with a handheld Raman reader, in performance evaluation studies.

Hepatitis C virus lacks an effective vaccine, partly due to the absence of suitable animal models for testing. Here, the authors develop a live-attenuated vaccine, using synonymous mutagenesis in rodent hepacivirus, and demonstrate induction of a protective T cell response and protection from chronic infection in rats.

The authors present a molecular classification of acute leukemia using 5-methylcytosine signatures, together with a neural network-based classifier for clinical use.

Here the authors show that mice exposed to a variety of pathogens initially have impaired innate type 2 responses to lung allergens, but reactivity resets over time, indicating that microbial experience does not stably inhibit innate immunity to allergens.

This study systematically explored the micellization of A-b-(B-alt-C)₂-b-A multiblock terpolymers using SCFT, revealing how block composition, interaction strength, and solvent selectivity govern diverse morphologies—including segmented vesicles, toroids, and cylinders. Symmetric and asymmetric solvent conditions yielded distinct BC-segmented structures, while poor solvent conditions led to hierarchical transitions. These insights offer design principles for functional materials like drug carriers by enabling precise control over self-assembled nanostructures.

A systematic review and meta-analysis of clinical trials investigating the efficacy and safety of obesity management medications reported tirzepatide and semaglutide to be the most effective in reducing body weight and obesity-related complications.

Here the authors show that genkwanin glycosides from Phaleria nisidai leaf extract improve glucose homeostasis by enhancing glucose uptake into adipose tissue, with effects comparable to metformin in a study with male mice with obesity and insulin resistance.

High IL1RL1 correlates with poor survival in acute myeloid leukemia. A stress-driven IL-33/IL1RL1 loop induces leukemogenesis and a tolerogenic immune environment. Targeting this axis with bispecific antibodies offers a promising treatment.

In a phase 1/2a umbrella trial in patients with glioblastoma matching targeted therapies according to tumor molecular profiling, temsirolimus plus radiotherapy improved PFS compared to standard of care in patients with phospho-mTOR activation.

The genomic instability phenotype characteristic of BRCA2-deficient cells is not fully mechanistically understood. Here the authors show BRCA2 inactivation destabilizes RPA-coated single-stranded DNA and leads to toxic non homologous end-joining events.

Glioblastoma can be classified based on IDH and TERT promoter mutations, but ~20% of glioblastoma do not have these mutations (TERTp^WT-IDH^WT glioblastoma). Here, the authors present a genetic landscape of TERTp^WT-IDH^WT glioblastoma, identifying a telomerase-positive subgroup driven by TERT-structural rearrangements and an ALT-positive subgroup with mutations in ATRX or SMARCAL1.

Append editing of ADP-ribosyl to thymine is used for precise modifications in bacteria and eukaryotes.

The authors report a computational framework for determining the meiotic/mitotic origin of nondisjunction (NDJ) in trisomies without parental data. Applying this to Down syndrome, they uncover links between NDJ error stage and leukemia genomics.

A first-in-human study of an antisense oligonucleotide targeting hepatitis B virus (HBV) RNA provides initial insights into this potential new therapeutic modality for individuals with chronic HBV infection.

Depletion of a transcriptional factor ZBTB11 using molecular glue degraders can overcome oxidative-phosphorylation-mediated KRAS inhibitor resistance in pancreatic ductal adenocarcinoma with low acute neurotoxicity.

Rat hepatitis E virus (HEV) can infect humans, but the extent of spillover isn’t well studied. Here the authors develop a serological test that distinguishes exposure to rat HEV from other HEV infection and show substantial spillover in a biodiversity hotspot in China. The method can support surveillance of rat HEV.

Pharmacologic inhibition of dihydroorotate dehydrogenase (DHODH) shows limited efficacy in pancreatic ductal adenocarcinoma (PDAC) models. Here the authors find that targeting the anti-apoptotic protein BCL-XL synergizes with DHODH inhibition in promoting apoptosis in PDAC cells, patient-derived organoids, and PDAC mouse models.

Around 1 in 136 pregnancies is lost due to a pathogenic small sequence variant genotype in the fetus.

Short-lived RNA folding intermediates have important roles in the folding of RNA. Here, the authors combine ¹⁵N relaxation dispersion NMR with chemical probing to visualise one of these intermediates, and are able to show it is a secondary structural switch, that might help with folding.

Prime editing can generate undesired editing outcomes. Here, authors describe a method for reducing both on-target and off-target imprecise editing outcomes of diverse prime editing modalities in different cell types with a combination of small molecules that inhibit both DNA-PK and PolΘ activity.

Metabolic and alcohol-related liver disease presents challenges in clinical trials due to complex pathophysiology. This Review discusses noninvasive imaging, serum biomarkers and adaptive designs as modalities to enhance patient-centric end points, aiming to refine diagnostics and improve drug development.

A pangenome of the Cannabis genus including 193 genomes demonstrates high variability in most of the genome but low diversity in cannabinoid synthesis genes and provides a resource for future genetic studies and crop optimization.

Plasma levels of liver enzymes provide insights into hepatic function and related diseases. Here, the authors perform a genome-wide association study on three liver enzymes, identifying genetic variants associated with their plasma concentration as well as links to metabolic and cardiovascular diseases.